الفهرس 
ACKNOWLEDREMENTOnly 14 pages are availabe for public view
 |  | from | 89 |  |  |
| | | from | 89 | | |
Abstract
As the therapeutic use of allogeneic bone marrow transplantation (BMT) advances rapidly for a wide variety of hematologic, metabolic and oncologic disorders, the graft versus host disease (GVHD) remains a major complication. Prior to T-cell depletion it was the major cause of transplat related mortality. A number of clinical studies showed that T-cell depletion from the marrow inoculum indeed decreased the incidence and severity of GVHD. However, this was achieved at the price of an increase in graft failure and leukemia relapse. Acute GVHD starts when donor T-cell react with alloantigens of the host. These T-cells release a variety of cytokines, all of which can activate large granular Lymphocytes (LGLs). Activated LGLs then engage in tissue destruction.. Previously we have shown that lnterleuktn 1 has pronounced effect on engraftment, as IL-I pre-treated lethally irradiated mice showed significantly accelerated hematopoietic recovery with enhancement of peripheral leukocytes, platelets and erythrocytes recovery. Testing of IL-I in GVHD systems was required to determine whether it could be tolerated in situation of allogeneic BMT with the risk of engraftment related difficulties and G VHD. In this part of our study, we have shown that IL-l administration, 20 hours before allogeneic bone marrow transplantation did not enhance the GVHD lesions. The tendency for the functional inhibition of T-cells rather than their depletion led as to evaluate on immuno modulatory regimen which is a clinical approach where we conducted a study on 40 patients with hematologic malignancies ( 11 AML , 15 ALL, 14 CML) who were undergoing myelo- ablative therapy and allogeneic BMT. The patient were classified into two groups. The first was given cyclosporin A (CSA) plus methylprednisolone (MP). The second was given CSA plus methotrexate (MIX). These two regimen were compared as regard their efficiency in GVHD prophylaxis. The results include our findings up to 1 decembre 1993 with a medianfollow up of 415 days (range 60 to 1975 days). No statistically significant difference was found between the two groups as regard the time to achieve granulocytes 0.5 x 109 I L or platelets 25 xl09 I L. On the other hand CSAIMP was more efficient in GVHD prophylaxis than CSA I MIX where 10 of 19 patients given CSA plus MP developed minimal or no GVHD (grades o and . I) compared to 4 of 21 patients given CSA plus MIX (p = 0.02) and 9 of 19 patients in CSAIMP group developed grades II to IV G VHD compared to 17 of 21 patients in the CSAIMIX group’ (p=O. 02).